First discovered in 1956 as a lower respiratory tract pathogen of children in their first year of life, human respiratory syncytial virus (RSV) is an enveloped, negative-sense single-stranded RNA virus belonging to the Pneumovirus genus within the Pneumovirinae subfamily of the family Paramyxoviridae. RSV is a major cause of lower respiratory tract infections, most commonly resulting in mild respiratory tract disease. However, infection with hRSV may result in severe bronchiolitis and pneumonia. In industrialized countries, RSV accounts for up to 70% of hospitalized bronchiolitis cases. Among infectious agents, respiratory syncytial virus is the second leading cause of death in infants. Worldwide, in 2010 alone, RSV is estimated to have caused over 230,000 deaths in children under 5 years of age, with the majority of deaths being in infants under the age of one (Lozano et al., Lancet (2012.) 380:2095-2128).
Currently, only supportive care is available to treat subjects infected with lower respiratory tract disease. In certain cases, a humanized neutralizing monoclonal antibody (mAb), palivizumab, can be used prophylactically, but is typically only used on infants considered at greatest risk for severe disease.
In the 1960s, a formalin-inactivated RSV vaccine was tested in infants and young children. Instead of protecting the airways of the infants upon natural infection, 80% of the vaccinated infants were hospitalized and two infants succumbed, while only 5% of the control vaccinated infants were hospitalized (Kim et al., Am J Epidemiol (1969) 89:422-434). As a result, the focus shifted to live, attenuated viral vaccines for protection and a great deal of effort has been spent developing these vaccines (Crowe et al., Vaccine (1995) 13:847-855; Karron et al., J Infect Dis (2005) 191:1093-1104; Karron et al., J Infect Dis (1997) 176:1428-1436; Kim et al., Pediatrics (1971) 48:745-755; Malkin et al., PLoS One (2013) 8:e77104; Wright et al., J Infect Dis (2000) 182:1331-1342; Wright et al., J Infect Dis (2006) 193:573-581).